Using Mendelian randomization to explore the gateway hypothesis: possible causal effects of smoking initiation and alcohol consumption on substance use outcomes.
Background and Aims: Initial use of drugs such as tobacco and alcohol may lead to subsequent more problematic drug use--the 'gateway' hypothesis. However, observed associations may be due to a shared underlying risk factor, such as trait impulsivity. We used bidirectional Mendelian randomization (MR...
| Publicado en: | Addiction Vol. 117; no. 3; pp. 741 - 751 |
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| Autores principales: | , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
Mar2022
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=155882850&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 155882850 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 09652140 AIO jtl: Addiction issn: 09652140 maglogo: Y pubinfo: dt: Mar2022 vid: 117 iid: 3 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 155882850 152702666 155882850 155882850 10.1111/add.15673 155882850 ppf: 741 ppct: 10 formats: fmt: @attributes: type: P tig: atl: Using Mendelian randomization to explore the gateway hypothesis: possible causal effects of smoking initiation and alcohol consumption on substance use outcomes. aug: au: Reed, Zoe E. Wootton, Robyn E. Munafò, Marcus R. affil: School of Psychological Science, University of Bristol, Bristol, UK sug: subj: Causal Attribution Smoking Complications Alcohol Drinking Substance Use Disorders Risk Factors Risk Assessment Substance Use Disorders Familial and Genetic Human Sensitivity and Specificity Nonexperimental Studies Genome Wide Association Study Cannabis Adverse Effects Substance Dependence Cocaine Adverse Effects Analgesics, Opioid Adverse Effects Confidence Intervals Descriptive Statistics Odds Ratio ab: Background and Aims: Initial use of drugs such as tobacco and alcohol may lead to subsequent more problematic drug use--the 'gateway' hypothesis. However, observed associations may be due to a shared underlying risk factor, such as trait impulsivity. We used bidirectional Mendelian randomization (MR) to test the gateway hypothesis. Design: Our main method was inverse-variance weighted (IVW) MR, with other methods included as sensitivity analyses (where consistent results across methods would raise confidence in our primary results). MR is a genetic instrumental variable approach used to support stronger causal inference in observational studies. Setting and participants: Genome-wide association summary data among European ancestry individuals for smoking initiation, alcoholic drinks per week, cannabis use and dependence, cocaine and opioid dependence (n = 1749-1 232 091). Measurements: Genetic variants for exposure. Findings: We found evidence of causal effects from smoking initiation to increased drinks per week [(IVW): ß = 0.06; 95% confidence interval (CI) = 0.03-0.09; P = 9.44 × 10-06], cannabis use [IVW: odds ratio (OR) = 1.34; 95% CI = 1.24-1.44; P = 1.95 × 10-14] and cannabis dependence (IVW: OR = 1.68; 95% CI = 1.12-2.51; P = 0.01). We also found evidence of an effect of cannabis use on the increased likelihood of smoking initiation (IVW: OR = 1.39; 95% CI = 1.08-1.80; P = 0.01). We did not find evidence of an effect of drinks per week on other substance use outcomes, except weak evidence of an effect on cannabis use (IVW: OR = 0.55; 95% CI = 0.16-1.93; P-value = 0.35). We found weak evidence of an effect of opioid dependence on increased drinks per week (IVW: ß = 0.002; 95% CI = 0.0005-0.003; P = 8.61 × 10-03). Conclusions: Bidirectional Mendelian randomization testing of the gateway hypothesis reveals that smoking initiation may lead to increased alcohol consumption, cannabis use and cannabis dependence. Cannabis use may also lead to smoking initiation and opioid dependence to alcohol consumption. However, given that tobacco and alcohol use typically begin before other drug use, these results may reflect a shared risk factor or a bidirectional effect for cannabis use and opioid dependence. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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